What is it about?
This study investigates why sleep loss makes the brain work more slowly. While the effects of sleep deprivation on attention and behavior are well known, the underlying biological mechanisms have remained unclear. Here, we focus on myelin, the insulating layer that surrounds nerve fibers and allows electrical signals to travel quickly through the brain. Using human brain imaging data and animal models, we show that sleep loss disrupts myelin integrity and slows the transmission of neural signals. We also identify changes in cholesterol metabolism within oligodendrocytes, the cells that produce myelin, as a key factor contributing to these effects. Together, our findings reveal a previously underappreciated role of myelin and oligodendrocytes in explaining how sleep loss impairs brain communication and behavior.
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Why is it important?
Sleep deprivation is increasingly common in modern society, yet its long-term effects on brain health are still poorly understood. Most research has focused on neurons and synapses, overlooking the role of glial cells and white matter. This study highlights myelin and oligodendrocytes as key contributors to brain performance during sleep loss, offering a new perspective on why cognitive and motor functions deteriorate when sleep is insufficient. By identifying cholesterol dysregulation in myelin as a potential mechanism, our findings open new avenues for understanding sleep-related brain vulnerability and suggest novel targets for preventing or mitigating the consequences of chronic sleep loss.
Perspectives
For a long time, the cognitive consequences of sleep loss have been attributed mainly to neuronal fatigue or synaptic dysfunction. Working on this study led us to reconsider that view and to look more closely at the role of oligodendrocytes and white matter. What surprised us most was how strongly sleep loss affected myelin biology and signal propagation, suggesting that sleep is essential not only for neuronal processing but also for maintaining the physical infrastructure that enables fast and precise brain communication. From this perspective, sleep deprivation does not simply impair information processing; it alters the conditions that allow the brain to operate efficiently and with proper timing. We hope this work contributes to a broader understanding of how sleep supports efficient neuronal signaling by shaping oligodendrocyte function.
Michele Bellesi
University of Camerino
Read the Original
This page is a summary of: Sleep loss induces cholesterol-associated myelin dysfunction, Proceedings of the National Academy of Sciences, January 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2523438123.
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